Multiple coronary embolisms in a woman with risk factors for thromboembolic disease

We report the case of a 33-years-old woman, smoker and taking oral contraceptives, who presented to the emergency room with an anterior ST-elevation myocardial infarction. Thrombolytic treatment was initiated and a few minutes after, chest pain returned and an inferior ST-segment-elevation infarction was diagnosed at that moment. Catheterization revealed multiple embolic occlusion of coronary branches. We discuss tests performed and pathophysiology of myocardial infarction in this patient.     

The potential role of the HIV-1 immunogen (Remune) as a therapeutic vaccine in the treatment of HIV infection

Immune-based therapies, such as therapeutic vaccination, that might preserve, restore, enhance and induce new HIV-specific immunologic responses are currently being explored. HIV-specific immunotherapy with Remune (The Immune Response Corp.) offers the opportunity to boost immune responses against HIV-1. The clinical trial program in a wide range of subjects has established the efficacy of Remune in stimulating an appropriate immune response in HIV-positive individuals. Furthermore, a recent unblinded study conducted in Europe has documented a significant effect of Remune on viral load. Evidence regarding clinical end points is more difficult to collect. The same studies have revealed no serious safety issues in a total of more than 2000 Remune-treated patients. It is therefore reasonable to suggest that the risk-benefit ratio of Remune could be positive.     

The Günther Tulip retrievable filter: prolonged temporary filtration by repositioning within the inferior vena cava

PURPOSE: To report experience with the retrievable Günther Tulip filter (GTF) as a means of temporary caval filtration for the prevention of pulmonary embolism (PE) with use of a technique that prolongs filter dwell time beyond 14 days. MATERIALS AND METHODS: Eighty-eight GTFs were implanted in 87 patients. The GTFs were placed with the intention of retrieval in all patients within 14 days after initial implantation. In 23 of the 87 patients (26%), there was a need to prolong temporary caval filtration beyond the recommended period of 14 days. This was successfully achieved with use of percutaneous techniques from the right internal jugular vein whereby the filter was repositioned to a different location within the inferior vena cava (IVC) before definitive device removal. RESULTS: Of 88 GTFs implanted in 87 patients, 70 were successfully retrieved and 18 were left in place permanently. Forty-seven filters in 46 patients were removed after initial implantation with no need for percutaneous repositioning within the IVC to prolong dwell time (mean dwell time, 13 days). In the 23 patients who required repositioning of 23 GTFs within the IVC to prolong temporary caval filtration, the mean dwell time was 34.8 days; the mean number of repositioning procedures was 1.5, the mean time between repositioning procedures was 13.8 days, and the mean fluoroscopy time was 4.4 minutes in patients in whom filter retrieval was attempted. One patient underwent placement and subsequent removal of the GTF twice for perioperative prophylaxis against PE on two separate occasions. No filters were misplaced in an unintended location or tilted (>15 degrees ) in relation to the main caval axis after deployment. In one patient, a GTF became permanently fixed in the IVC 16 days after initial implantation and could not be removed percutaneously. Nine patients had mild or moderate-sized cervical hematomas. One patient had recurrent asymptomatic PE 2 months after filter insertion. CONCLUSION: Dwell times of 14 days can be achieved in most patients before device removal. Prolongation of the dwell time beyond 14 days can be safely and easily achieved by performing percutaneous repositioning of the device within the IVC via a jugular approach.     

Irinotecan in the treatment of advanced colorectal cancer in patients pretreated with Fluorouracil-based chemotherapy: a study to determine recommendable therapeutic dosage

Because no consensus exists regarding recommendable dose levels for irinotecan, an intrapatient dose escalation phase I-II study was initiated in previously treated patients with colorectal cancer. Survival was a secondary endpoint. Thirty-five consecutive patients with progressive disease after 5-fluorouracil-based chemotherapy were enrolled to receive irinotecan starting from 250 mg/m2/3 weeks and rising to currently used therapeutic doses. In total, 162 cycles were administered. The median tolerable dose was 250 mg/m2. Twelve patients (34%) were unable to tolerate doses greater than 250 mg/m2, 10 patients (28%) presented toxicity at 250 mg/m2 and 2 patients tolerated only 200 mg/m2. Three patients (9%) had partial response. The major adverse reactions were grade III-IV diarrhea, grade II-III nausea/vomiting, grade II-III neutropenia, and grade II-III anaemia in 28%, 48%, 11%, and 17% of the patients, respectively. Median survival time and time to progression were 8 and 3 months, respectively. The current irinotecan dose of 350 mg/m2/3 weeks appears unacceptably toxic and, hence, a lower dose needs to be considered. The response rates obtained are similar to the results observed in phase III studies, and its activity appears not to be adversely affected with this treatment scheme.     

Complete tumor prevention by engineered tumor cell vaccines employing nonviral vectors

We report that 100% mice survival after tumor challenge is achieved with cytokine-engineered cells employing nonviral lipoplexes and without using viral vectors. We describe this effect with cytokine-secreting tumor cell vaccines, based on cell clones or fresh transfected cells. Tumor cells were transfected with murine granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-4 plasmids employing the cationic lipid DOTAP, were irradiated (150 Gy) and kept frozen until use. The transfection efficacy was analyzed by qRT-PCR and flow cytometry. Vaccination induced potent antitumor rejection, resulting in 100% mice survival. Furthermore, the antitumor immunity was long lasting, since a two-fold survival delay was observed in mice after tumor rechallenge (6 months later). While cell clones secreting GM-CSF were the most effective in wild-type tumor cell rejection, little or no effect was observed with clones secreting IL-4. We found similar antitumor efficacy employing fresh transfected cells by nonviral procedures, demonstrating that cells genetically modified by nonviral vectors (both clones and fresh transfected cells) are a safe and efficient tool for antitumor vaccines. These vaccines allow us to achieve the highest antitumor efficacy based on nonviral gene therapy techniques. In addition, the vaccination success with fresh transfected cells simplifies the procedure and provides new insights into the clinical application of nonviral gene therapy procedures.     

Relative Reactivity of Dihydropyridine Derivatives to Electrogenerated Superoxide Ion in DMSO Solutions: A Voltammetric Approach

Purpose. To evaluate the reaction of a large series of pharmacologically significant 1,4-dihydropyridine (1,4-DHP) compounds with superoxide (O^·– ₂) in dimethylsulfoxide using differential pulse voltammetry and controlled potential electrolysis. Methods. Differential pulse voltammetry was used to track the consumption of O^·– ₂, and controlled potential electrolysis was used to electrogenerate O^·– ₂. Results. With the addition of 1,4-DHP, the oxidation peak current of O^·– ₂ decreased concentration dependently, suggesting that 1,4-DHP reacts with O^·– ₂, that is, 1,4-DHP scavenges O^·– ₂ in dimethylsulfoxide. Conclusions. A very easy and direct voltammetric procedure to study the relative reactivity of different 1,4-DHP with O^·– ₂ is proposed. Using the proposed method we have found that all commercial 1,4-DHP reacts with O^·– ₂. The following order of rates was obtained: felodipine vitamin E > isradipine > nimodipine > furnidipine > nitrendipine > nisoldipine > nifedipine. Furthermore, it was demonstrated that the hydrogen at the N-position of 1,4-DHP compounds could be released as a proton in the presence of O^·– ₂, thus the electrogenerated O^·– ₂ worked as a proton acceptor to 1,4-DHP.     

Lateral approach to the sciatic nerve in the popliteal fossa: a comparison between 1.5% mepivacaine and 0.75% ropivacaine

BACKGROUND AND OBJECTIVES: Ropivacaine and mepivacaine are commonly used local anesthetics for peripheral nerve blockade. The purpose of the present study was to compare onset time, quality of anesthesia, and duration of analgesia with ropivacaine 0.75% and mepivacaine 1.5% for lateral popliteal nerve block. METHODS: Fifty American Society of Anesthesiologists (ASA) physical status I or II patients scheduled for foot and ankle surgery with calf tourniquet under lateral popliteal sciatic nerve block were randomly assigned to receive 30 mL of either ropivacaine 0.75% or mepivacaine 1.5%. Time required for onset of sensory and motor block, resolution of motor blockade, onset of postsurgical pain, and time of first analgesic medication were recorded. RESULTS: The 2 groups were similar with regard to demographic variables and duration of surgery. Onset of sensory and motor block was significantly shorter in the mepivacaine group (9.9 +/- 3.3 min and 14.7 +/- 3.6 min, respectively) than in the ropivacaine group (18.1 +/- 6.1 min and 23.6 +/- 5.5 min, respectively) (P < 0.001). Resolution of motor block occurred later in the ropivacaine group than in the mepivacaine group (P < 0.001), and duration of postoperative analgesia was significantly longer in the ropivacaine group (19 +/- 3.4 h) compared with the mepivacaine group (5.9 +/- 1.1 h) (P < 0.001). Analgesic requirements were higher in mepivacaine group than in the ropivacaine group (P < 0.001). There were 2 failed blocks, one in each group. CONCLUSIONS: Both ropivacaine and mepivacaine provided effective sciatic nerve blockade. Mepivacaine 1.5% displayed a significantly shorter onset time than ropivacaine 0.75%. Postoperatively, ropivacaine 0.75% resulted in longer-lasting analgesia and less need for oral pain medication.     

Calculation of the gastric absorption rate constants of 5-substituted barbiturates through theR m values or substituent ΔR m constants in reversed-phase partition chromatography

A linear correlation between the logarithm of the in situgastric absorption rate constants (k_a)of 5-substituted barbiturates and their R_m values in selected reversed-phase partition chromatographic systems is demonstrated, as well as between the log k_a and the R_m derived parameters. On the basis of the chromatographic behavior of 14 closely related compounds of this series, the substituent R_m constants for the main functional groups are calculated, so that the gastric absorption constants of nontested barbiturates can be predicted with close approximation. Predicted R_m and log k_a values show an excellent correlation with log 1/C values taken from pharmacological literature data. The migration mechanisms involved in reversed-phase partition chromatography are discussed in connection with the results obtained with other types of partition systems and with bulk-phase solvents. The possible relationships between chromatographic parameters and absorption rate constants found from absorption sites other than the stomach are outlined; as well as the advantages and limitations of the procedure.     

Registro Español de Desfibrilador Automático Implantable. XV Informe Oficial de la Sección de Electrofisiología y Arritmias de la Sociedad Española de Cardiología (2018)

Introduction and objectivesThis article presents the data corresponding to automated implantable cardioverter-defibrillator (ICD) implants in Spain reported to the Spanish Registry in 2018.MethodsThe data in this registry include both primary implants and generator replacements and were gathered from a data collection sheet voluntarily completed by implantation centers.ResultsIn 2018, 6421 implant sheets were received compared with 7077 reported by Eucomed (European Confederation of Medical Suppliers Associations). This represents data on 90.7% of the devices implanted in Spain. Compliance ranged between 99.6% for the field “name of the implanting hospital” and 12.4% for “population of residence”. A total of 173 hospitals reported their data to the registry, representing a slight decrease compared with hospitals participating in 2017 (n = 181).ConclusionsAfter the reduction in ICD implants in 2017, the number of implants increased in 2018, with the highest number of ICDs implanted in Spain. The total number of implants remains much lower than the European Union average, with substantial differences between autonomous communities.